Apolipoprotein B100

Author: Lorenzo Schiaffino
Date: 20/09/2013



Apolipoprotein B100 (512 kDa), encoded by ApoB gene, is the main apolipoprotein of LDL which is responsible for carrying cholesterol to tissues. Apolipoproteins are amphipathic in nature, because they have both hydrophobic and hydrophilic regions, and can interact both with the lipids of the lipoprotein and with the aqueous environment.
In mammals ApoB gene encodes for two forms of apoB:

  • ApoB100 (512 kDa) represents the full-length protein containing 4536 residues and is the exclusive form synthesized in human liver. This protein is the majior component of LDL.
  • ApoB48 (250 kDa) is synthesized in the small intestine of all mammals, as well as in the liver of certain species: it is colinear with the amino terminal 2152 residue s of the full-length form. This protein is the majior component of chylomicrons.

Mutations or alterated levels of these lipoprotein alter the cholesterol and lipid metabolism


In human the ApoB gene is localized on the 2 chromosome (location Chromosome 2: 21,224,301-21,266,945).
Official Symbol: APOB
Other Aliases: FLDB, LDLCQ4
Other Designations:apo B-100; apoB-100; apoB-48; apolipoprotein B (including Ag(x) antigen); apolipoprotein B-100; apolipoprotein B48; mutant Apo B 100

GeneCardsApolipoprotein B
Your Favorite Gene SigmaApolipoprotein


ApoB100 is divided into five distinct regions.

These domains are not entirely homogenous, as there appears to be some admixture of amphipathic alpha-helices within the beta-domains, and vice versa.

  • Amphipathic beta sheets:
    • The first alpha-beta-1 motif partecipate in lipid accumulation;
    • Direct contact of the hydrophobic face of amphipathic beta sheets with the neutral lipid core determine lipid organization, lipolysis, and lipid transfer;
    • The beta sheets motif determine the LDL particle diameter;
  • Amphipathic alpha helical:
    • The alpha-1 and alpha-2 modulate the surface pressure decreases that occur as the particle decreases in size during lipoprotein metabolism and lipid exchange;

Moreover, Near to the beta-2 domain there is the receptor-binding domain, in which are present numerous proline-rich domain.
ApoB100 tertiary structure is still unknown. It is a very large protein and it show not significant homology to any know protein in the databases. Recently it has been proposed a theoretical 3D model by using the computational approaches and, for this reason, can be made some general obsversations: only the N-terminal domain is globular in its shape, while all the other domains are characterized by an extended overall conformation.

Protein Aminoacids Percentage

There are many similarities between the sequence of ApoB and Vitellogenin (it doesn't exist in human). This protein belongs to a family of several lipid transport proteins.


Two forms of ApoB exist in mammals: in normal human subjects, plasma residence time of chylomicrons is very short (minutes to hours) compared with that of LDL (2 days).
ApoB48 is a crucial protein needed to delivery the dietary lipid from small intestine to liver, whereas ApoB100 partecipates in the transport and delivery of endogenous plasma cholesterol.
A common ApoB gene produces two distinct protein isoforms: this process is called RNA editing. A site-specific C-to-U editing reaction produces a UAA stop codon and translational termination of intestinal ApoB mRNA at residue 2152, the form referred to as apoB48. This site- specific C-to-U conversion (hydrolytic deamination) is mediated by an enzyme complex containing a single catalytic subunit apobec-1.

C-to-U editing of ApoB mRNA is a precise reaction, and this specificity is due to the presence of an 11-nucleotide cassette (UGAUCAGUAUA), which is located optimally downstream of the target C (mutations in this cassette reduce or abolish in vitro RNA editing). Other requirements include an AU-rich context and the presence of distal efficiency elements both 5’ and 3’ of the edited C.
Editing levels of ApoB mRNA have been shown to vary in response to changes in diet. exposure to alcohol and hormone levels.
ApoB100 is synthetized in the endoplasmic reticulum of liver cell. After the translation ApoB100 is palmitoylated, this process bind fatty acids, such as palmitic acid, to cystein and is essential for proper assembly of the hydrophobic core of the lipoprotein particle.
In the end the ApoB100 proteins are degraded via the cytoplasmic proteasome or luminal proteases.


ApoB100 is involved in the LDL transports cholesterol from the liver to the tissues of the body. LDL cholesterol is therefore considered the "bad" cholesterol.

Apo B exposes a domain that can interact with LDL receptors (receptors for Apo B-100) that are located in the liver but also in extrahepatic tissues.
The binding of LDL and the receptor in the hepatocyte surface triggers an endocytosis process (“receptor-mediated-endocytosis”), with the formation of endosomes. Changes in PH provoke the dissociation between the lipoprotein and the receptor, the receptor returns to the membrane while the endosome merges with a lysosome; lysosome enzymes hydrolyze the LDL proteins, the cholesterol esters and other lipids.
The signal that a cell needs cholesterol is expressed through the presence of LDL receptors in the cell surface: the synthesis of LDL receptors inhibited by high intracellular concentrations of cholesterol.

KEGG PathwaysApoB pathway


The expression of ApoB100 is regulated by 3'-UTR and 5'-UTR motifs. There are many potential cis-trans interactions of these motifs with RNA binding proteins that permit the translation of ApoB100. It seems that putative 5′UTR motifs are important for optimal translation of the apoB message whereas the presence of the 3′UTR appears to attenuate wild-type expression


The detections of the ApoB allow us to quantify the risk to contract vascular diseases. In fact there is a relation between high levels of ApoB and atherosclerosis and this makes ApoB detection in the blood a better risk marker than the LDL dosage. Generally the normal values of the normal values of the ApoB in the plasma is 35-100 mg/100ml.
There is a clear relation between the concentration of ApoB100 in the blood and the number of LDL because each of these particles contins just one Apolipoprotein B.
High levels of ApoB100 in blood entail an high number of LDL lipoproteins, but they don't give any information about their contents of lipids and in particular cholesterol because the particles may have different quantities or triglycerides and cholesterol.
The ApoB levels are linked to the ApoA1 concentration. Lower is the ratio APOA1/APOB higher is the cardiovascular diseases risk.

The diseases characterized by ApoB values altered are several (monogenic hypercholesterolemia , hypertriglyceridemia, hypocholesterolemia ) but only few of these are induced by ApoB mutations.
Here below there is a short mention of some deseases caused by mutation of ApoB.
Familial defective apolipoprotein B-100 - FH2/FDB:
It is characterized by a codominant autosomal mutation on the gene of ApoB100 .
It has a frequency between 1/500 and 1/700. More than 8 missense mutation on binding domain of ApoB100 have been identified more.
The gene has 29 exons and the most frequent mutation occurs on the 26th exon: ( glutamine instead of arginine p 3500 ) .
This desease is similar to classical familial hypercholesterolemia and is diagnosed as FH1 in 3/5 of patients. This hypercholesterolemia is less severe than FH1 and atherosclerotic processes are slowed down. The 95 of patients have borderline cholesterol levels below the 95th percentile. Homozygotes FDB have cholesterol values ​​similar to heterozygous FH.
There are other mutations of ApoB100 in P3500: in addition to glutamine in place of arginine, tryptophan instead of arginine (unusual but frequent in Asians); cysteine ​​in place of arginine (rare, reduces the affinity bound between LDL and its receptor of 50%).
Familial Hypobetalipoproteinemia FHBL:
It is induced by codominant autosomal mutation on exon 26 of ApoB gene. This desease causes reduced level of VLDL and LDL due to low level of ApoB.
Heterozygotes have 25-50% of normal levels, homozygotes have very low levels but are very rare.
In the homozygous null allele FHBL patient there is absence of LDL and VLDL (undetectable) and differs from homozygous mutated allele FHBL patient for the determination of triglycerides.
The frequency of heterozygous hypobetalipoproteinemia is between 1/500 and 1/1000 but it could be higher. In homozygous FHBL is common acanthocytosis. In all of these pathologies is essential dosage of LDL for diagnosis.
There are FHBL-causing mutations in the APOB gene. Two thirds of the mutations are nonsense and frameshift mutations in exon 26.

2014-01-22T16:21:33 - Gianpiero Pescarmona

apoB-100 thyroid hormone binding

ApoB-100-containing lipoproteins are major carriers of 3-iodothyronamine in circulation. 2012

Approximately 99% of the circulating thyroid hormones are bound to plasma proteins, including three major thyroid hormone-binding proteins, and the question arises as to whether circulating T(1)AM is also bound to serum factors.

Binding of thyroxine to human plasma low density lipoprotein through specific interaction with apolipoprotein B (apoB-100). 1989

The observed thyroid hormone binding property of lipid-complexed apoB-100 and the knowledge that receptors for the apolipoprotein exist in various tissues suggest a possible physiological role in thyroid hormone transport.


SPB10_HUMAN adiacente APOB100


Hydrophobic cluster analysis (HCA) of the hormone-binding domain of receptor proteins. 1989

A new technique of protein sequence analysis, namely, Hydrophobic Cluster Analysis (HCA), has been used to align and compare the sequences of proteins belonging to the receptor superfamily (steroid, thyroid hormone and retinoic acid receptors) and serpin superfamily (corticosteroid binding globulin (CBG) and alpha 1-antitrypsin (alpha 1-AT]. By matching up clusters of hydrophobic amino-acids that oftenmost correspond to identifiable secondary structures (alpha-helices, beta-strands etc.), it has been possible to deduce the following information on the secondary structures of these proteins:

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